Highly Efficient Binary and Remote Asymmetric Induction from a Single Allyltin Reagent with a Chiral Carbamate Moiety

Abstract

Carbamate-protected chiral allyltin reagent was found to afford either syn- or anti-homoallyl alcohol via 1,4-remote asymmetric induction in the reaction with various aldehydes depending on the applied Lewis acid, TiCl₄-THF or SnCl₄, respectively. The both stereocontrols were so effective that the selectivities higher than 90% were realized in most cases.

Key words

allylations - Lewis acids - protecting groups - stereo­selective synthesis - tin

References

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• Thomas group and Dias group also reported similar asymmetric induction. See:
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• 9a Stereochemistry of the products was determined by the derivatization and by the comparison with the previously reported compounds. See ref. 3-5. Also refer to: Nishigaichi Y. Takuwa A. Jodai A. Tetrahedron Lett.  1991,  32:  2383 
• 9b

  As a typical example, ¹H NMR spectra of compound 3d (R = C₆H₅) were shown below.
  Compound syn-3d (R = C₆H₅): 1.36 (d, 3 H, J = 6.6 Hz), 2.45 (dd, 1 H, J = 13.9, 10.0 Hz), 2.55 (dd, 1 H, J = 13.9, 2.7 Hz), 2.94 (s, 3 H), 2.96 (s, 3 H), 4.10 (d, 1 H, J = 2.4 Hz), 4.84 (ddd, 1 H, J = 10.3, 2.7, 2.4 Hz), 5.04 (br s, 1 H), 5.16 (br s, 1 H), 5.19 (q, 1 H, J = 6.6 Hz), 7.43 (m, 5 H).
  Compound anti-3d (R = C₆H₅): 1.38 (d, 3 H, J = 6.6 Hz), 2.42 (dd, 1 H, J = 13.8, 9.3 Hz), 2.50 (dd, 1 H, J = 13.8, 4.8 Hz), 2.93 (s, 3 H), 2.97 (s, 3 H), 3.67 (d, 1 H, J = 3.2 Hz), 4.96 (br s, 1 H), 5.02 (ddd, 1 H, J = 9.3, 4.8, 3.2 Hz), 5.13 (br s, 1 H), 5.16 (q, 1 H, J = 6.6 Hz), 7.36 (m, 5 H).

• 10 Nishigaichi Y. Fujimoto M. Nakayama K. Takuwa A. Hamada K. Fujiwara T. Chem. Lett.  1992,  2339 
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• 16 Recently, Markó group reported a successful application of the carbamate protection to the allylmetal chemistry. See: Dubost C. Leroy B. Markó IE. Tinant B. Declercq J.-P. Bryans J. Tetrahedron  2004,  60:  7693 

7

Both reagents 2c and 2d were prepared readily from the corresponding alcoholic reagent and methyl chloroformate or dimethylcarbamoyl chloride, respectively.

8

Typical Procedure for SnCl ₄ -Mediated Reaction.
To a dry CH₂Cl₂ solution (2 mL) of SnCl₄ (0.3 mmol) was added 2d (0.3 mmol) at -78 °C under nitrogen. After 2 min, an aldehyde (0.2 mmol) in CH₂Cl₂ (2 mL) was added and the mixture was stirred at the same temperature for 30 min. After addition of diluted HCl solution, the products were extracted with Et₂O, which was then washed with H₂O and sat. NaHCO₃ solution, and dried over anhyd Na₂SO₄. The condensed mixture was purified on silica gel TLC to isolate the products.

11

Reaction of benzaldehyde by TiCl₄ without Et₂O gave a diastereoisomeric mixture of syn/anti = 4:6, which means the transmetallation promoted the preferential formation of the anti-isomer.

12

Typical Procedure for TiCl ₄ -THF-Mediated Reaction.
To a mixture of an aldehyde (0.2 mmol), THF (0.6 mmol) and dry CH₂Cl₂ (2 mL) was added TiCl₄ (0.2 mmol) at
-78 °C under nitrogen. Then, 2d (0.3 mmol) in 2 mL of CH₂Cl₂ was added and the mixture was stirred for 1 h at
-78 °C. Work up procedure was the same as that for SnCl₄-mediated reaction in ref. 8.

14

To LiAlH₄ (49 mg, 1.3 mmol) in 2 mL of dry Et₂O was added an ethereal solution of AlCl₃ (1.3 mmol) at 0 °C under nitrogen. After being stirred for 5 min, the carbamate (0.13 mmol) dissolved in 2 mL of dry Et₂O was added and the mixture was stirred for 1 h at 0 °C. After addition of diluted aq HCl solution sat. by NaCl, the product was extracted with Et₂O four times and the combined extracts were washed with brine, dried and condensed. The residue was purified on silica gel TLC.